The safety of azithromycin in the treatment of adults with community-acquired respiratory tract infections

The comparative safety of azithromycin was assessed in adult patients (> or =12 years) with community-acquired respiratory tract infections. Of 3229 patients evaluated, 1616 received azithromycin 500 mg once daily for 3 days and 1613 received standard regimens of amoxycillin, amoxycillin/clavulanic acid, cefaclor, clarithromycin, or roxithromycin. A similar incidence of treatment-related adverse events occurred with azithromycin (10.3%) and comparators (11.5%). Significantly fewer patients were withdrawn from azithromycin than comparator treatment (0.4 versus 2.1%; P=0.0001). Most adverse events were mild/moderate in intensity and affected the gastrointestinal system. Azithromycin was as well tolerated as other antibiotics commonly used for bacterial infections in adults.     

Update on the cardiac safety of moxifloxacin

Cardiac safety was compared in patients receiving moxifloxacin and other antimicrobials in a large patient population from Phase II-IV randomized active-controlled clinical trials. Moxifloxacin 400 mg once-daily monotherapy was administered orally (PO) or sequentially (intravenous/oral, IV/PO). Across 64 trials, 21,298 patients received PO therapy (10,613 moxifloxacin, 10,685 comparators) while 6846 received sequential IV/PO therapy (3431 moxifloxacin, 3415 comparators). Treatment-emergent cardiac adverse event (AE) rates were similar for moxifloxacin and comparators in PO (6.6% vs 5.8%) and IV/PO (11.0% vs 12.0%) trials. Treatment-emergent cardiac adverse drug reactions were rare in PO (moxifloxacin 3.2% vs comparators 2.4%) and IV/PO (moxifloxacin 1.4% vs comparators 1.5%) patients. There were five (<0.02%) treatment-emergent drug-related deaths due to cardiac events out of 28,144 patients; one PO patient died treated with comparators, one patient died treated with IV/PO moxifloxacin, and three patients died after treatment with IV/PO comparators. Only one case of treatment-related non-fatal torsade de pointes occurred in the comparator arm. Incidence rates of cardiac AEs remained low in populations at elevated risk of cardiac events predisposed to QTc prolongation (i.e. community-acquired pneumonia patients admitted to the intensive care unit and/or mechanical ventilation, patients with documented prolongation of baseline QTc interval, women, and patients ≥ 65 years old). There was no evidence of unexpected cardiac events. After moxifloxacin treatment, an expected small prolongation in QTcB and QTcF was found. This analysis of numerous clinical trials shows the favorable cardiac safety profile of moxifloxacin, when used appropriately and according to its label, versus other antibiotics.     

Amoxicillin/clavulanic acid: a review of its use in the management of paediatric patients with acute otitis media

Amoxicillin/clavulanic acid (Augmentin), Augmentin ES-600 is a well established, orally administered combination of amoxicillin (a semisynthetic antibacterial agent) and clavulanic acid (a beta-lactamase inhibitor). Amoxicillin/clavulanic acid shows good activity against the main pathogens associated with acute otitis media (AOM), including penicillin-susceptible and -intermediate strains of Streptococcus pneumoniae, and beta-lactamase producing strains of Haemophilus influenzae and Moraxella catarrhalis. It has moderate activity against penicillin-resistant S. pneumoniae; a high-dose formulation has been developed with the aim of providing better coverage for penicillin-resistant strains. Amoxicillin/clavulanic acid (conventional formulations, mostly 40/10 mg/kg/day in three divided doses) produced clinical response rates similar to those of oral cephalosporin comparators and similar to or significantly greater than those for intramuscular ceftriaxone in randomised trials in paediatric patients with AOM (mean age approximately 2 to 5 years). Clinical response rates were generally similar for amoxicillin/clavulanic acid and macrolide comparators (mean patient age approximately 1 to 6 years), although significantly better clinical and bacteriological responses were seen versus azithromycin in one randomised trial (mean patient age approximately 1 year). The high-dose formulation of amoxicillin/clavulanic acid (90/6.4 mg/kg/day in two divided doses) eradicated a high proportion of penicillin-resistant S. pneumoniae (penicillin MICs 2 or 4 mg/L) in a large noncomparative trial in children with AOM (upper limit of the US indication for S. pneumoniae is 2 mg/L). Amoxicillin/clavulanic acid is generally well tolerated. A low total incidence of adverse events (3.6%) and no serious events were reported from a large paediatric postmarketing study. The most frequently reported adverse events in children are mild gastrointestinal disturbances. Diarrhoea is generally less frequent with twice-daily than with three-times-daily treatment. The new high-dose formulation showed similar tolerability to a conventional twice-daily formulation (45/6.4 mg/kg/day) in a well controlled trial. CONCLUSIONS: Amoxicillin/clavulanic acid is a well established broad-spectrum antibacterial treatment which is effective and well tolerated in the treatment of AOM in paediatric patients. The high-dose combination should prove valuable in treating AOM caused by penicillin-intermediate and -resistant S. pneumoniae (approved in the US for penicillin MIC < or =2 mg/L). Based on recent recommendations and the available data, high-dose amoxicillin/clavulanic acid can be considered a treatment of choice for recurrent or persistent paediatric AOM (after failure of amoxicillin alone) where involvement of resistant pathogens is suspected.     

Efficacy and safety of topical ciprofloxacin/dexamethasone versus neomycin/polymyxin B/hydrocortisone for otitis externa

OBJECTIVES: To compare the efficacy and safety of ciprofloxacin 0.3%/dexamethasone 0.1% (CIP/DEX) otic suspension with that of neomycin 0.35%/polymyxin B 10,000 IU/mL/hydrocortisone 1.0% (N/P/H) otic suspension in patients with acute otitis externa (AOE). STUDY DESIGN: Randomized, observer-masked, parallel-group, multicenter study. Patients were randomized to 7 days treatment with either CIP/DEX 3-4 drops twice daily or N/P/H 3-4 drops three times daily. POPULATION: Patients of either sex and older than 1 year, with a clinical diagnosis of mild, moderate, or severe AOE and intact tympanic membranes were recruited to participate. OUTCOMES MEASURED: Signs and symptoms of AOE, including ear inflammation, tenderness, edema and discharge (assessed on Days 3, 8 [End-of-Therapy] and 18 [Test-of-Cure]); microbiologic eradication (presumed or documented); and frequency of adverse events. RESULTS: Patients enrolled numbered 468. In culture-positive patients who met the inclusion criteria (N = 396), clinical cure rates at Day 18 were significantly higher with CIP/DEX than with N/P/H (90.9% vs. 83.9%; p = 0.0375), as were microbiologic eradication rates (94.7% vs. 86.0%; p = 0.0057). In addition, the clinical response was significantly better with CIP/DEX than with N/P/H at Days 3 and 18 (p = 0.0279 and p = 0.0321, respectively), as was the reduction in ear inflammation at Day 18 (p = 0.0268). Both preparations were well tolerated in pediatric and adult patients. CONCLUSIONS: 7 days treatment with CIP/DEX otic suspension administered twice daily is clinically and microbiologically superior to N/P/H otic suspension administered 3 times daily in the treatment of mild to severe AOE, and is equally well tolerated.     

Voriconazole: in the treatment of invasive aspergillosis

Voriconazole, a broad-spectrum triazole antifungal agent, inhibits the cytochrome P450-dependent enzyme 14-alpha-sterol demethylase, thereby disrupting the fungal membrane and stopping fungal growth. The drug shows excellent in vitro activity against Aspergillus spp., including itraconazole- and amphotericin B-resistant A. fumigatus isolates. At 12 weeks, 52.8% of voriconazole recipients achieved a successful outcome (complete or partial response) versus 31.6% of amphotericin B recipients in a randomised, nonblind trial in 392 patients (aged > or =12 years) with invasive aspergillosis. Patients received intravenous voriconazole (6 mg/kg once every 12 hours on day 1, then 4 mg/kg once every 12 hours for > or =7 days; patients could then be switched to oral voriconazole 200mg once every 12 hours) or intravenous amphotericin B (1 to 1.5 mg/kg/day for > or=14 days). At the investigators' discretion, those who failed to respond to or experienced toxicity with the initial randomised drug could be switched to other licensed antifungal therapy. Voriconazole was generally well tolerated. The most common treatment-related adverse events were transient visual disturbances (approximately 30% of patients) and skin rashes (6%). Voriconazole was generally better tolerated than amphotericin B; voriconazole recipients experienced significantly (p < 0.02 both comparisons) fewer treatment-related adverse events or serious adverse events. The incidence of visual disturbances was significantly (p < 0.001) higher with voriconazole than amphotericin B treatment.     

Oral beclometasone dipropionate in the treatment of active ulcerative colitis: a double-blind placebo-controlled study

AIM: To evaluate efficacy and safety of oral beclometasone dipropionate (BDP) when added to 5-ASA in the treatment of patients with active ulcerative colitis. METHODS: In a 4-week, placebo-controlled, double-blind study, patients with extensive or left-sided mild to moderate active ulcerative colitis were randomized to receive oral 5-ASA (3.2 g/day) plus BDP (5 mg/day) or placebo. Clinical, endoscopic and histologic features, and haematochemical parameters were recorded at baseline and at the end of the study. RESULTS: One hundred and nineteen patients were enrolled and randomly treated with BDP plus 5-ASA (n = 58) or placebo plus 5-ASA (n = 61). Both treatment groups showed a statistically significant decrease of disease activity index (DAI) and histology score at the end of treatment (P = 0.001, each). DAI score was lower in the BDP group than in the placebo group (P = 0.014), with more patients in clinical remission in the BDP group (58.6% vs. 34.4%, P = 0.008). Serum cortisol levels significantly decreased in BDP group vs. baseline (P = 0.002), but without signs of pituitary-adrenal function depletion. A low incidence of adverse events was observed in both groups. CONCLUSIONS: Oral BDP in combination with oral 5-ASA is significantly more effective than 5-ASA alone in the treatment of patients with extensive or left-sided active ulcerative colitis.     

Azithromycin versus comparative therapy for the treatment of community acquired pneumonia

A 3-day course of azithromycin was compared with the 10 days of other antibiotics, which general practitioners routinely use as therapy for community acquired pneumonia (CAP). The study was a prospective open labelled, randomised, multicentre, comparative study from five family clinics. Patients with clinical and radiological evidence of pneumonia were included. The pneumonia resolved in 98.4% (61/62) of patients treated with azithromycin and in 87% (40/46) of patients treated with other antibiotics (P < 0.017). Restitution of normal function at home (2.3 +/- 1.2 and 4.3 +/- 2.6 days) and return to work (3.4 +/- 2.0 and 5.5 +/- 3.1 days) was more rapid among the group treated with azithromycin ( P < 0.001). Three days of azithromycin was more convenient and cost effective than the comparators used to treat pneumonia.     

Azithromycin 1.5% ophthalmic solution: in purulent bacterial or trachomatous conjunctivitis

The second-generation macrolide azithromycin is available as a 1.5% ophthalmic solution for use in the treatment of bacterial or trachomatous conjunctivitis. This article reviews the pharmacological properties of azithromycin 1.5% ophthalmic solution and its clinical efficacy and tolerability in patients with purulent bacterial conjunctivitis or trachomatous conjunctivitis caused by Chlamydia trachomatis. Azithromycin 1.5% ophthalmic solution had good in vitro activity against Haemophilus influenzae and C. trachomatis, and achieved good concentrations in tear samples from healthy volunteers. Azithromycin 1.5% ophthalmic solution for 3 days (1 drop twice daily) was noninferior to tobramycin 0.3% ophthalmic solution for 7 days (1 drop every 2 hours) in paediatric and adult patients with purulent bacterial conjunctivitis, with regard to clinical cure and bacteriological resolution on day 9, in a randomized, investigator-masked, multicentre study. In children with trachomatous inflammation, 3-day treatment with azithromycin 1.5% ophthalmic solution was noninferior to a single dose of azithromycin oral suspension, with regard to clinical cure rate in the worst eye at 60 days, in a randomized, double-masked, multicentre study. Azithromycin 1.5% ophthalmic solution was well tolerated in patients with bacterial or trachomatous conjunctivitis. Most events were of mild to moderate severity.     

Efficacy and safety of topical ciprofloxacin/dexamethasone versus neomycin/polymyxin B/ hydrocortisone for otitis externa

SUMMARY

Objectives: To compare the efficacy and safety of ciprofloxacin 0.3%/dexamethasone 0.1% (CIP/DEX) otic suspension with that of neomycin 0.35%/polymyxin B 10?000?IU/mL/hydrocortisone 1.0% (N/P/H) otic suspension in patients with acute otitis externa (AOE).

Study Design: Randomized, observer-masked, parallel-group, multicenter study. Patients were randomized to 7 days treatment with either CIP/DEX 3–4 drops twice daily or N/P/H 3–4 drops three times daily.

Population: Patients of either sex and older than 1 year, with a clinical diagnosis of mild, moderate, or severe AOE and intact tympanic membranes were recruited to participate.

Outcomes Measured: Signs and symptoms of AOE, including ear inflammation, tenderness, edema and discharge (assessed on Days 3, 8 [End-of-Therapy] and 18 [Test-of-Cure]); microbiologic eradication (presumed or documented); and frequency of adverse events.

Results: Patients enrolled numbered 468. In culture-positive patients who met the inclusion criteria (N = 396), clinical cure rates at Day 18 were significantly higher with CIP/DEX than with N/P/H (90.9% vs. 83.9%; p = 0.0375), as were microbiologic eradication rates (94.7% vs. 86.0%; p = 0.0057). In addition, the clinical response was significantly better with CIP/DEX than with N/P/H at Days 3 and 18 (p = 0. 0279 and p = 0. 0321, respectively), as was the reduction in ear inflammation at Day 18 (p = 0.0268). Both preparations were well tolerated in pediatric and adult patients.

Conclusions: 7 days treatment with CIP/DEX otic suspension administered twice daily is clinically and microbiologically superior to N/P/H otic suspension administered 3 times daily in the treatment of mild to severe AOE, and is equally well tolerated.     

Improved tonsillar disposition of azithromycin following a 3-day oral treatment with 20 mg kg(-1) in paediatric patients.

The present study was performed in order to compare azithromycin concentrations in tonsils of paediatric patients treated with different dose regimens of this antibiotic. Sixty-four children, scheduled to undergo surgical removal of tonsils, were treated with azithromycin 10 or 20 mgkg(-1) daily as oral suspension for 3 days. Samples of blood and tonsil were collected during surgery at days 0.5, 2.5, 4.5, 6.5 or 8.5 after the last dose. Azithromycin concentrations were measured by reversed phase high-performance liquid chromatography. In patients treated with 10 mgkg(-1), the highest concentrations of azithromycin were detected in plasma and tonsils at day 0.5 and 2.5, respectively. Consistent drug levels could be measured in tonsils up to 8.5 days. After administration of 20 mgkg(-1), azithromycin tonsillar concentrations were higher than those obtained with 10 mgkg(-1) up to day 6.5, whereas plasma levels did not differ significantly. The present results indicate that an improved tonsillar distribution of azithromycin can be achieved when this antibiotic is administered for 3 days at doses higher than 10 mgkg(-1) daily. These findings give pharmacokinetic support to the suggestion that increments of azithromycin dosing might ensure enhanced therapeutic levels at infective sites of the upper respiratory tract.     

艾司西酞普兰与西酞普兰治疗抑郁症的对照研究

目的评价艾司西酞普兰治疗抑郁症的有效性和安全性。方法选择126例抑郁症患者,试验组63例,口服艾司西酞普兰:1-2周口服10 mg,3-6周剂量可调10-20 mg;对照组63例,口服西酞普兰:1-2周口服20 mg,3-6周剂量可调20-40 mg。疗程6周,以十七项汉密尔顿抑郁量表(HAMD-17)、汉密尔顿焦虑量表(HAMA)和临床总体印象量表(CGI)进行疗效评价;以不良事件、实验室检查和心电图检查等评价安全性。结果共106例患者完成研究,试验组52例,对照组54例。试验组与对照组6周末有效率(82.7%vs 88.9%,P=0.484)、痊愈率(36.5%vs.27.8%,P=0.360),2组差异无统计学意义(P>0.05)。HAMA和CGI的评分在各时间点2组相比差异无统计学意义(P>0.05)。试验组与对照组不良反应发生率(17.5%vs 30.2%,P=0.07)差异无统计学意义。结论艾司西酞普兰治疗抑郁症安全有效,与西酞普兰相当,不良反应较轻。     

The efficacy and safety of aripiprazole as adjunctive therapy in major depressive disorder: a second multicenter, randomized, double-blind, placebo-controlled study

Nonresponse to one or more antidepressants is common and an important public health problem. This study evaluated the efficacy and safety of adjunctive aripiprazole or placebo to standard antidepressant therapy (ADT) in patients with major depressive disorder who showed an inadequate response to at least 1 and up to 3 historical and 1 additional prospective ADT. The study comprised a 7-28-day screening, an 8-week prospective treatment, and a 6-week randomization phase. During prospective treatment, patients experiencing a major depressive episode (17-item Hamilton Rating Scale for Depression total score > or = 18) received single-blind adjunctive placebo plus clinicians' choice of ADT (escitalopram, fluoxetine, paroxetine controlled-release, sertraline, or venlafaxine extended-release). Subjects with inadequate response were randomized to adjunctive placebo (n = 190) or adjunctive aripiprazole (n = 191) (starting dose 5 mg/d, dose adjustments 2-20 mg/d, mean end-point dose of 11.0 mg/d). The primary efficacy endpoint was the mean change in Montgomery-Asberg Depression Rating Scale total score from end of prospective treatment phase to end of randomized treatment phase (last observation carried forward). Mean change in Montgomery-Asberg Depression Rating Scale total score was significantly greater with adjunctive aripiprazole than placebo (-8.5 vs -5.7; P = 0.001). Remission rates were significantly greater with adjunctive aripiprazole than placebo (25.4% vs 15.2%; P = 0.016) as were response rates (32.4% vs 17.4%; P < 0.001). Adverse events occurring in 10% of patients or more with adjunctive placebo or aripiprazole were akathisia (4.2% vs 25.9%), headache (10.5% vs 9.0%), and fatigue (3.7% vs 10.1%). Incidence of adverse events leading to discontinuation was low (adjunctive placebo [1.1%] vs adjunctive aripiprazole [3.7%]). Aripiprazole is an effective and safe adjunctive therapy as demonstrated in this short-term study for patients who are nonresponsive to standard ADT.     

A multiple dose study of prasugrel (CS-747), a novel thienopyridine P2Y12 inhibitor, compared with clopidogrel in healthy humans

AIMS: This double-blind, placebo-controlled trial was designed to evaluate the pharmacodynamics, pharmacokinetics, safety, and tolerability of prasugrel (CS-747, LY640315), a novel thienopyridine P2Y(12) ADP receptor antagonist compared with clopidogrel, during multiple oral dosing in healthy subjects. METHODS: Thirty subjects received placebo, prasugrel 5 mg, 10 mg, or 20 mg, or clopidogrel 75 mg orally, daily for 10 days. Platelet aggregation, bleeding time, and prasugrel metabolites were measured and adverse events were recorded. RESULTS: Inhibition of ADP-induced platelet aggregation reached steady state by day 3 following prasugrel 10 and 20 mg compared with 5 days for clopidogrel 75 mg or prasugrel 5 mg. Compared with placebo, at 24 h after the last dose of study drug, inhibition of platelet aggregation using (20 microm) ADP was significantly higher in the prasugrel 10 mg group (58.2 +/- 4.9% vs. 9.2 +/- 4.0%, P < 0.001) with no difference in the clopidogrel group (15.7 +/- 6.8% vs. 9.2 +/- 4.0%, P = 0.78). With 5 microm ADP, inhibition of platelet aggregation with prasugrel 10 mg and clopidogrel 75 mg was significantly higher than with placebo (prasugrel 10 mg, 70.5 +/- 4.7%; clopidogrel 75 mg, 36.5 +/- 9.0%; vs. placebo, 11.3 +/- 5.1%; P < 0.0001 and P = 0.02). On day 10 at 4 h postdose, bleeding time was prolonged with prasugrel 10 mg (prasugrel 10 mg, 706 +/- 252 s vs. placebo, 221 +/- 38 s, P = 0.05) but not with clopidogrel (283 +/- 56 s, P = 0.98). There were no clinically significant bleeding events, serious adverse events, or discontinuations of the study drug. CONCLUSIONS: Compared with clopidogrel 75 mg, prasugrel 10 mg and 20 mg daily for 10 days resulted in more rapid, more consistent, and higher levels of platelet inhibition.     

Single-dose azithromycin versus erythromycin or amoxicillin for Chlamydia trachomatis infection during pregnancy: a meta-analysis of randomised controlled trials

This review aimed to compare data regarding the effectiveness and safety of azithromycin with alternative regimens in the treatment of pregnant women with Chlamydia trachomatis infection. PubMed and Scopus databases were searched to identify relevant randomised controlled trials (RCTs). The main analysis focused on comparison of azithromycin with erythromycin. In a secondary analysis, azithromycin was compared with erythromycin or amoxicillin. Eight RCTs studying 587 pregnant women with microbiologically documented C. trachomatis infection were included in the meta-analysis. Overall, there was no difference between azithromycin and erythromycin regarding treatment success in intention-to-treat patients (pooled odds ratio (OR)=2.66, 95% confidence interval (CI) 0.69-10.29) or in clinically evaluated patients (OR=1.46, 95% CI 0.56-3.78). Furthermore, azithromycin was associated with fewer gastrointestinal adverse events (OR=0.11, 95% CI 0.07-0.18), fewer total adverse events (OR=0.11, 95% CI 0.07-0.18), a smaller proportion of patients who withdrew from the study (OR=0.12, 95% CI 0.04-0.37) and better compliance (OR=23.7, 95% CI 9.34-60.14) than erythromycin. The results of the secondary analysis comparing azithromycin with erythromycin or amoxicillin were similar to those of the main analysis. In conclusion, azithromycin was associated with similar effectiveness but less adverse events compared with erythromycin or amoxicillin in the treatment of pregnant women with C. trachomatis infection.     

Retrospective analysis of the safety profile of oral moxifloxacin in elderly patients enrolled in clinical trials.

BACKGROUND AND OBJECTIVE: As aging is associated with physiological changes, including renal and hepatic insufficiency, and a higher risk of drug interactions, special attention needs to be directed towards the safety of medications in the elderly. The objective of this analysis was to evaluate the safety of oral moxifloxacin in elderly patients who were enrolled in clinical trials and to compare these results to those of other commonly used antibacterials. METHODS: Safety data from 27 prospective, randomised, comparative phase II/III trials of oral moxifloxacin included in the Bayer clinical trial database were pooled and analysed by age group (<65 years of age, 65-74 years of age, > or = 75 years of age) and by treatment group (moxifloxacin vs comparator). The primary endpoints included rates of treatment-emergent adverse events (all adverse events regardless of causality), drug-related adverse events, drug-related serious adverse events, deaths and premature discontinuations because of a treatment-emergent adverse event. A treatment by age group interaction test was used to determine if the comparison between moxifloxacin and the comparator group in the incidence rates of any treatment-emergent or drug-related adverse events were affected by increasing age. RESULTS: Of the 12 231 patients who had valid safety data, 6270 had been treated with oral moxifloxacin and 5961 with a comparator antibacterial. The most frequently used comparators were cefuroxime and clarithromycin. Most patients (n = 9671) were <65 years of age (4939 moxifloxacin, 4732 comparator); 1636 patients were 65-74 years of age (842 moxifloxacin, 794 comparator); and 924 patients were > or = 75 years of age (489 moxifloxacin, 435 comparator). The treatment by age group interaction test revealed that the comparison of drug-related adverse event rates between the moxifloxacin and comparator group were not affected by increasing age (p = 0.43). Rates of premature termination between the moxifloxacin and comparator treatment groups also did not increase with age (p = 0.552). No arrhythmias related to corrected QT (QTc) interval prolongation were reported following oral moxifloxacin or comparator treatment in this large group of young and elderly patients. Overall, the number of deaths was similar between the treatment groups (17 moxifloxacin, 19 comparator). CONCLUSIONS: Drug-related adverse event rates associated with oral moxifloxacin or the comparator therapy used in these studies did not significantly increase with advancing age. This pooled analysis suggests that oral moxifloxacin can be safely used in elderly patients with characteristics consistent with those enrolled into the clinical trials.     

The Cardiovascular Effects of Treatment with Hydroxychloroquine and Azithromycin

Hydroxychloroquine combined with azithromycin has been investigated for activity against coronavirus disease 2019 (COVID-19), but concerns about adverse cardiovascular (CV) effects have been raised. This study evaluated claims data to determine if risks for CV events were increased with hydroxychloroquine alone or combined with azithromycin. We identified data from 43,752 enrollees that qualified for analysis. The number of CV events increased by 25 (95% confidence interval [CI]: 8, 42, p=0.005) per 1000 people per year of treatment with hydroxychloroquine alone compared with pretreatment levels and by 201 (95% CI: 145, 256, p<0.001) events per 1000 people per year when individuals took hydroxychloroquine and azithromycin. These rates translate to an additional 0.34 (95% CI: 0.11, 0.58) CV events per 1000 patients placed on a 5-day treatment with hydroxychloroquine monotherapy and 2.75 (95% CI: 1.99, 3.51) per 1000 patients on a 5-day treatment with both hydroxychloroquine and azithromycin. The rate of adverse events increased with age following exposure to hydroxychloroquine alone and combined with azithromycin. For females aged 60 to 79 years prescribed hydroxychloroquine, the rate of adverse CV events was 0.92 per 1000 patients on 5 days of therapy, but it increased to 4.78 per 1000 patients when azithromycin was added. The rate of adverse CV events did not differ significantly from zero for patients 60 years of age or younger. These data suggest that hydroxychloroquine with or without azithromycin is likely safe in individuals under 60 years of age if they do not have additional CV risks. However, the combination of hydroxychloroquine and azithromycin should be used with extreme caution in older patients.     

阿奇霉素序贯疗法治疗急性盆腔炎性疾病的临床观察

目的探讨阿奇霉素序贯疗法治疗盆腔炎性疾病的疗效和安全性。方法 300例急性盆腔炎性疾病患者进行序贯疗法(前期静脉注射阿奇霉素500mg,每日1次,1~2d;后改为口服阿奇霉素250mg,每日1次,共治疗7d)。治疗结束当日、治疗后第15天及第29天评估临床有效率和细菌根除率。结果病例样本最常见的病原体为:沙眼衣原体(60株)、二路普氏菌(50株)、无乳链球菌(35株)、淋球菌(30株)和厌氧消化链球菌(30株)。临床进行临床有效率和细菌根除率分析,治疗结束当日,沙眼衣原体感染者分别为100%(60/60)和72.7%(40/55),二路普氏菌感染者分别为90%(45/50)和80%(40/50),无乳链球菌感染者分别为85.7%(30/35)和57.1%(20/35),淋球菌感染者分别为100%(30/30)和33.3%(10/30),厌氧消化链球菌感染者分别为83.3%(25/30)和83.3%(25/30)。临床有效率,第15天和第29天各菌种治疗有效率均无显著变化。细菌根除率和后期根除率均有所提高。相关的常见不良反应是腹泻、注射部位疼痛和恶心,均为轻度或中度。结论阿奇霉素序贯疗法能够有效治疗盆腔多种病原微生物,包括喹诺酮耐药菌引起的盆腔炎,且患者耐受性良好。     

Efficacy and safety of moxifloxacin as antibacterial prophylaxis for patients receiving autologous haematopoietic stem cell transplantation: a randomised trial

Patients receiving high-dose chemotherapy with autologous peripheral blood stem cell transplantation (PBSCT) are at high risk of infections, especially bacteraemia. A prospective, double-blind, randomised, placebo-controlled, single-centre, pilot study was performed on oral moxifloxacin 400mg versus placebo for preventing bacteraemia in PBSCT recipients. Patients received moxifloxacin or placebo for the duration of neutropenia or until emergence of fever or other infections necessitating intravenous antibiotic treatment. Of 68 patients included in the trial, 2 were excluded from the trial before taking their first dose. The remaining 66 patients were eligible for evaluation in the intention-to-treat analysis set. Neutropenia with an absolute neutrophil count of <500cells/μL developed in 30 moxifloxacin-treated patients (88.2%) and 21 patients in the placebo group (65.6%) (P<0.03). Nine patients (26.5%) and eight patients (25.0%), respectively, were prematurely discontinued from study treatment. Breakthrough bacteraemia occurred in 3 moxifloxacin-treated patients (8.8%) and 9 patients in the placebo group (28.1%) (P=0.042). The time period until fever was 9.5 days [95% confidence interval (CI) 8.06-10.94 days) and 7.69 days (95% CI 6.51-8.85 days), respectively (P=0.0499). There was no difference in adverse events or toxicities between the groups. Moxifloxacin prevented bacteraemia and shortened febrile episodes in patients receiving autologous PBSCT. No significant increase of adverse events in the moxifloxacin arm was observed, possibly due to the rather small sample size.     

阿奇霉素治疗慢性前列腺炎优于复方磺胺甲噁唑

目的：探讨阿奇霉素对慢性前列腺炎的疗效和安全性。方法：慢性前列腺炎病人８７例,年龄３２ａ±ｓ９ａ（２１～４７ａ）,随机分成２组,分别服用阿奇霉素（４４例）０．５ｇ,ｐｏ,ｑｄ及复方磺胺甲唑（ＳＭＺＣｏ）２片（４３例）,ｐｏ,ｂｉｄ,疗程６ｄ。服药前及服药后１,２ｗｋ分别行前列腺液（ＥＰＳ）常规及病原学检查,并监测血、尿常规及肝、肾功能。结果：阿奇霉素组病人痊愈率４８％和有效率８０％均高于ＳＭＺＣｏ组４２％和６５％（Ｐ＜０．０５）。２药对各类致病菌的清除率分别为７９％及６５％（Ｐ＜０．０５）;不良反应发生率分别为７％和１４％（Ｐ＜０．０５）。结论：阿奇霉素比ＳＭＺＣｏ对慢性前列腺炎具有较佳疗效,且服用方便,不良反应少。     

磺达肝癸钠治疗非急诊血运重建急性心肌梗死的效果与安全性

目的探讨急性心肌梗死且未行急诊血运重建患者使用磺达肝癸钠的近期疗效和安全性。方法480例急性心肌梗死患者（未接受急诊再灌注治疗）按随机数随机分为依诺肝素组和磺达肝癸钠组,各240例。依诺肝素组给予依诺肝素1mg／kg（年龄〈75岁）或0．75mg／kg皮下注射（年龄≥75岁）,1次／12h;磺达肝癸钠组给予磺达肝癸钠2．5mg／kg皮下注射,1次／24h,均连用5～9d。比较2组治疗9d内主要不良心脏事件（MACE）、严重出血发生率和30d及6个月随访情况。结果治疗9d轻微出血和总出血磺达肝癸钠组均较依诺肝素组减少[19例（7．9％）比44例（18．3％）和25例（10．4％）比57例（23．7％）,风险比（HR）分别为0．412、0．413,95％置信区间（CI）0．241～0．706、0．258～0．662,P=0．001、P=0．000]。随访1个月,磺达肝癸钠组MACE发生率低于依诺肝素组[37例（15．4％）比59例（24．6％）,HR=0．600,95％CI为0．398～0．905,P=0．015],至6个月时差异无统计学意义[62例（25．8％）比77例（32．1％）,HR=0．751,95％C10．537～1．049,P=0．098]。结论磺达肝癸钠治疗早期未行血运重建急性心肌梗死患者近期疗效优于依诺肝素,且出血并发症少。